Pub Date : 2025-11-05DOI: 10.1038/s41409-025-02735-7
Vanderson Rocha, Myriam Labopin, Anna Maria Raiola, Raynier Devillier, Stefania Bramanti, Fabio Ciceri, Jose Luiz Diez-Martin, Yener Koc, Johanna Tischer, Simona Sica, Mohamad Mohty, Zafer Gülbas, Aleksandr Kulagin, Lucía López Corral, Jacques Emmanuel Galimard, Anna Sureda, Annalisa Ruggeri, from the Cellular Therapy & Immunobiology Working Party of the European Society for Blood and Marrow Transplantation
Few studies analyzed the impact of bone marrow (BM) or peripheral blood stem cells (PBSC) on outcomes after haploidentical transplantation using post-cyclophosphamide (Haplo-PTCY). We analyzed 8854 adults with malignant disorders, given a first Haplo-PTCY. BM cells was used in 2914 and PBSC in 5940 patients. Multivariate models were built adjusting for the statistical differences between the 2 groups. Median follow-up time for survivors in the BM and PBSC groups were 48 and 30 months, respectively. Neutrophil Engraftment was observed in 92.4% of BM and 93.7% of PBSC recipients (p = 0.01). In a multivariate analysis, use of PBSC compared to BM, was associated with higher incidence of acute (HR:1.53; p < 0.0001) and chronic GVHD (HR:1.34; p < 10-3), increased non-relapse mortality (HR:1.22; p = 0.002), similar risk of relapse (HR:1.02; p = 0.79), and decreased overall survival (OS)(HR:1.13; p = 0.008); progression-free survival (PFS)(HR:1.11; p = 0.024) and GVHD-Relapse free survival (GRFS) (HR:1.2; p < 10–3). In conclusion, use of BM cells is associated with better outcomes compared to PBSC after Haplo-PTCY. Future studies should investigate better GVHD prophylaxis in the PBSC-Haplo-PTCY setting and the association of measured T-cell or other subpopulations of lymphocyte content in the PBSC graft.
很少有研究分析骨髓（BM）或外周血干细胞（PBSC）对使用后环磷酰胺（haploi - ptcy）进行单倍体移植后预后的影响。我们分析了8854名患有恶性疾病的成年人，首次进行了单倍型ptcy检查。2914例使用BM细胞，5940例使用PBSC细胞。建立多变量模型，调整两组间的统计学差异。BM组和PBSC组幸存者的中位随访时间分别为48个月和30个月。92.4%的BM和93.7%的PBSC受者有中性粒细胞移植（p = 0.01）。在一项多变量分析中，与BM相比，使用PBSC与更高的急性发病率相关(HR:1.53; p
{"title":"Use of bone marrow cells is associated with improved outcomes when compared to peripheral blood stem cell after haplo-identical transplants with post transplant cyclophosphamide, a study from of the CTIWP-EBMT","authors":"Vanderson Rocha, Myriam Labopin, Anna Maria Raiola, Raynier Devillier, Stefania Bramanti, Fabio Ciceri, Jose Luiz Diez-Martin, Yener Koc, Johanna Tischer, Simona Sica, Mohamad Mohty, Zafer Gülbas, Aleksandr Kulagin, Lucía López Corral, Jacques Emmanuel Galimard, Anna Sureda, Annalisa Ruggeri, from the Cellular Therapy & Immunobiology Working Party of the European Society for Blood and Marrow Transplantation","doi":"10.1038/s41409-025-02735-7","DOIUrl":"10.1038/s41409-025-02735-7","url":null,"abstract":"Few studies analyzed the impact of bone marrow (BM) or peripheral blood stem cells (PBSC) on outcomes after haploidentical transplantation using post-cyclophosphamide (Haplo-PTCY). We analyzed 8854 adults with malignant disorders, given a first Haplo-PTCY. BM cells was used in 2914 and PBSC in 5940 patients. Multivariate models were built adjusting for the statistical differences between the 2 groups. Median follow-up time for survivors in the BM and PBSC groups were 48 and 30 months, respectively. Neutrophil Engraftment was observed in 92.4% of BM and 93.7% of PBSC recipients (p = 0.01). In a multivariate analysis, use of PBSC compared to BM, was associated with higher incidence of acute (HR:1.53; p < 0.0001) and chronic GVHD (HR:1.34; p < 10-3), increased non-relapse mortality (HR:1.22; p = 0.002), similar risk of relapse (HR:1.02; p = 0.79), and decreased overall survival (OS)(HR:1.13; p = 0.008); progression-free survival (PFS)(HR:1.11; p = 0.024) and GVHD-Relapse free survival (GRFS) (HR:1.2; p < 10–3). In conclusion, use of BM cells is associated with better outcomes compared to PBSC after Haplo-PTCY. Future studies should investigate better GVHD prophylaxis in the PBSC-Haplo-PTCY setting and the association of measured T-cell or other subpopulations of lymphocyte content in the PBSC graft.","PeriodicalId":9126,"journal":{"name":"Bone Marrow Transplantation","volume":"61 1","pages":"75-81"},"PeriodicalIF":5.2,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41409-025-02735-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145450936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-28DOI: 10.1038/s41409-025-02734-8
Andre Manfred Willasch, Claire Horgan, Christina Peters, Adriana Balduzzi, Jean-Hugues Dalle, Marco Zecca, Ali Al-Ahmari, Franco Locatelli, Cecile Renard, Oana Mirci-Danicar, Charlotte Jubert, Maura Faraci, Evgenios Gossetis, Gérard Michel, Edoardo Benedetti, Richard Mitchell, Franca Fagioli, Renata Formankova, Giovanna Lucchini, Kanchan Rao, Alessandra Biffi, Fanny Rialland, Amos Toren, Marc Ansari, Arnaud Dalissier, Selim Corbacioglu, Katharina Kleinschmidt, Peter Bader, Maud Ngoya, Jacques-Emmanuel Galimard, Krzysztof Kalwak
Allogeneic haematopoietic stem cell transplantation (HSCT) is an essential treatment component for high-risk paediatric acute myeloid leukaemia (AML), but the choice of the optimal conditioning regimen remains controversial. We compared outcomes of two widely used myeloablative regimens, BuCy (Busulfan, Cyclophosphamide) versus BuCyMel (Busulfan, Cyclophosphamide, Melphalan) in children aged under 2 years undergoing HSCT in 1st complete remission (CR1). This international, registry-based study was conducted by the Paediatric Diseases Working Party (PDWP) of the European Society for Blood and Marrow Transplant (EBMT) and included patients transplanted from 2000-2022. 335 patients, transplanted across 98 centres, were included, 185 (55.2%) patients received BuCy and 150 patients (44.8%) received BuCyMel. BuCyMel was associated with significantly better leukaemia-free survival (LFS) (4 y: 74.8% vs 58.8%, HR 0.52 (95%CI: 0.33-0.82), p = 0.004) and overall survival (OS) (4 y: 77.9% vs 66.2%, HR 0.55 (95%CI: 0.33-0.91), p = 0.02) compared with BuCy, and significantly lower relapse incidence (4 y: 18.1% BuCyMel vs 31.5% BuCy, HR 0.50 (95%CI 0.29-0.87), p = 0.01). Four-year non-relapse mortality (NRM) did not differ between groups. Our results suggest that BuCyMel is a better conditioning regimen compared with BuCy in children aged under 2 years undergoing HSCT for CR1 AML.
同种异体造血干细胞移植（HSCT）是高风险儿童急性髓性白血病（AML）的重要治疗组成部分，但最佳调节方案的选择仍然存在争议。我们比较了两种广泛使用的清髓方案BuCy （Busulfan, Cyclophosphamide）和BuCyMel （Busulfan, Cyclophosphamide, Melphalan）在2岁以下接受HSCT的第一次完全缓解（CR1）的儿童中的结果。这项国际注册研究由欧洲血液和骨髓移植学会（EBMT）儿科疾病工作组（PDWP）开展，纳入了2000-2022年移植的患者。在98个中心移植的335例患者中，185例（55.2%）患者接受BuCy， 150例（44.8%）患者接受BuCyMel。与BuCy相比，BuCyMel具有更好的无白血病生存率（LFS） （4y: 74.8% vs 58.8%, HR 0.52 (95%CI: 0.33-0.82), p = 0.004）和总生存率（OS） （4y: 77.9% vs 66.2%, HR 0.55 (95%CI: 0.33-0.91), p = 0.02），显著降低复发率（4y: 18.1% BuCyMel vs 31.5% BuCy, HR 0.50 (95%CI 0.29-0.87), p = 0.01）。4年非复发死亡率（NRM）组间无差异。我们的研究结果表明，与BuCy相比，BuCyMel在2岁以下接受HSCT治疗CR1 AML的儿童中是一种更好的调节方案。
{"title":"Comparison of outcomes of BuCy versus BuCyMel as preparation for allogeneic HSCT in infants with acute myeloid leukemia in first complete remission: a multicenter study from the EBMT PDWP","authors":"Andre Manfred Willasch, Claire Horgan, Christina Peters, Adriana Balduzzi, Jean-Hugues Dalle, Marco Zecca, Ali Al-Ahmari, Franco Locatelli, Cecile Renard, Oana Mirci-Danicar, Charlotte Jubert, Maura Faraci, Evgenios Gossetis, Gérard Michel, Edoardo Benedetti, Richard Mitchell, Franca Fagioli, Renata Formankova, Giovanna Lucchini, Kanchan Rao, Alessandra Biffi, Fanny Rialland, Amos Toren, Marc Ansari, Arnaud Dalissier, Selim Corbacioglu, Katharina Kleinschmidt, Peter Bader, Maud Ngoya, Jacques-Emmanuel Galimard, Krzysztof Kalwak","doi":"10.1038/s41409-025-02734-8","DOIUrl":"10.1038/s41409-025-02734-8","url":null,"abstract":"Allogeneic haematopoietic stem cell transplantation (HSCT) is an essential treatment component for high-risk paediatric acute myeloid leukaemia (AML), but the choice of the optimal conditioning regimen remains controversial. We compared outcomes of two widely used myeloablative regimens, BuCy (Busulfan, Cyclophosphamide) versus BuCyMel (Busulfan, Cyclophosphamide, Melphalan) in children aged under 2 years undergoing HSCT in 1st complete remission (CR1). This international, registry-based study was conducted by the Paediatric Diseases Working Party (PDWP) of the European Society for Blood and Marrow Transplant (EBMT) and included patients transplanted from 2000-2022. 335 patients, transplanted across 98 centres, were included, 185 (55.2%) patients received BuCy and 150 patients (44.8%) received BuCyMel. BuCyMel was associated with significantly better leukaemia-free survival (LFS) (4 y: 74.8% vs 58.8%, HR 0.52 (95%CI: 0.33-0.82), p = 0.004) and overall survival (OS) (4 y: 77.9% vs 66.2%, HR 0.55 (95%CI: 0.33-0.91), p = 0.02) compared with BuCy, and significantly lower relapse incidence (4 y: 18.1% BuCyMel vs 31.5% BuCy, HR 0.50 (95%CI 0.29-0.87), p = 0.01). Four-year non-relapse mortality (NRM) did not differ between groups. Our results suggest that BuCyMel is a better conditioning regimen compared with BuCy in children aged under 2 years undergoing HSCT for CR1 AML.","PeriodicalId":9126,"journal":{"name":"Bone Marrow Transplantation","volume":"61 1","pages":"67-74"},"PeriodicalIF":5.2,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145387149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-23DOI: 10.1038/s41409-025-02736-6
Ioanna Lazana, Konstantinos Gkirkas, Ioannis Konstantellos, Chrisovalanto Chatzidimitriou, Aggeliki Karagiannidou, Georgia Gkolfinopoulou, Maria Stamouli, Spiros Chondropoulos, Panagiotis Tsirigotis
Post-transplant cyclophosphamide (PTCy) has been explored as GvHD prophylaxis in matched related and unrelated donor transplants with encouraging outcomes, although at the cost of increased toxicity. A prospective, single-center study was conducted to assess the safety and efficacy of reduced-dose PTCy (15 or 25 mg/kg), combined with low-dose alemtuzumab and cyclosporin for GvHD prophylaxis, following 9/10 mismatched unrelated peripheral blood stem cell transplantation (MMUD PBSCT). Low-dose PTCy resulted in significantly reduced cumulative incidence (CI) of acute GvHD (aGvHD) grade II–IV and III–IV compared to control, without affecting relapse rates. Furthermore, the PTCy-group exhibited significantly lower non-relapse mortality (NRM), improved overall survival (OS) and GvHD-free/relapse-free survival (GRFS) (19% vs 45%, 63% vs 35% and 48% vs 25% for PTCy and control groups, respectively). PTCy-15 subgroup exhibited significantly increased NRM compared to PTCy-25 subgroup. However, this effect was counterbalanced by a significant decrease in the CI of relapse, overall resulting in similar OS and GRFS between the two subgroups. This is one of the first studies showing not only the efficacy of low-dose PTCy in GvHD prevention in the MMUD allo-PBSCT setting, but also the ability to tailor PTCy dosing based on relapse risk, allowing for a personalized approach to GvHD prevention.
{"title":"Low-dose post-transplant cyclophosphamide in combination with low-dose alemtuzumab for graft-versus-host-disease prevention in mismatched unrelated allogeneic stem cell transplantation is associated with improved outcomes and reduced toxicity","authors":"Ioanna Lazana, Konstantinos Gkirkas, Ioannis Konstantellos, Chrisovalanto Chatzidimitriou, Aggeliki Karagiannidou, Georgia Gkolfinopoulou, Maria Stamouli, Spiros Chondropoulos, Panagiotis Tsirigotis","doi":"10.1038/s41409-025-02736-6","DOIUrl":"10.1038/s41409-025-02736-6","url":null,"abstract":"Post-transplant cyclophosphamide (PTCy) has been explored as GvHD prophylaxis in matched related and unrelated donor transplants with encouraging outcomes, although at the cost of increased toxicity. A prospective, single-center study was conducted to assess the safety and efficacy of reduced-dose PTCy (15 or 25 mg/kg), combined with low-dose alemtuzumab and cyclosporin for GvHD prophylaxis, following 9/10 mismatched unrelated peripheral blood stem cell transplantation (MMUD PBSCT). Low-dose PTCy resulted in significantly reduced cumulative incidence (CI) of acute GvHD (aGvHD) grade II–IV and III–IV compared to control, without affecting relapse rates. Furthermore, the PTCy-group exhibited significantly lower non-relapse mortality (NRM), improved overall survival (OS) and GvHD-free/relapse-free survival (GRFS) (19% vs 45%, 63% vs 35% and 48% vs 25% for PTCy and control groups, respectively). PTCy-15 subgroup exhibited significantly increased NRM compared to PTCy-25 subgroup. However, this effect was counterbalanced by a significant decrease in the CI of relapse, overall resulting in similar OS and GRFS between the two subgroups. This is one of the first studies showing not only the efficacy of low-dose PTCy in GvHD prevention in the MMUD allo-PBSCT setting, but also the ability to tailor PTCy dosing based on relapse risk, allowing for a personalized approach to GvHD prevention.","PeriodicalId":9126,"journal":{"name":"Bone Marrow Transplantation","volume":"61 1","pages":"59-66"},"PeriodicalIF":5.2,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145353665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-22DOI: 10.1038/s41409-025-02739-3
Federica Galaverna, Jan Styczynski, Per Ljungman
This review aims to show new insights into the prevention and management of cytomegalovirus (CMV) infections in pediatric hematopoietic stem cell transplant (HCT) recipients. CMV-seropositivity in pediatric recipients/donors (R/D) is lower than in adults. Post-HCT CMV infection rates appear to follow the hierarchy: R+/D− > R+/D+ > R−/D+. Pediatric risk factors are similar to those seen in adults and include recipient CMV-seropositivity, HCT from an alternative donor, older age, and graft-versus-host-disease. In case of CMV-seropositive pediatric recipients, donor CMV-seronegativity is associated with lower survival and higher non-relapse mortality. Until recently, preemptive treatment has been the standard approach for managing pediatric post-HCT CMV infection. The successful introduction of letermovir in the prophylaxis of CMV infection has changed this approach and has become the standard of care in adults. Clinical data and recent FDA/EMA approval of letermovir in children are also providing a breakthrough in pediatric CMV disease prevention. Pre-emptive treatment remains the preferred approach in case of clinically significant CMV infection in both adults and children; meanwhile, new available options such as maribavir and broader application of viral-specific T-cells represent valid strategies for the management of refractory/resistant CMV infection, offering a less-toxic therapeutic alternative to conventional, still effective, antivirals.
{"title":"Changing scenario in prevention and management of CMV infections in pediatric hematopoietic stem cell transplant patients","authors":"Federica Galaverna, Jan Styczynski, Per Ljungman","doi":"10.1038/s41409-025-02739-3","DOIUrl":"10.1038/s41409-025-02739-3","url":null,"abstract":"This review aims to show new insights into the prevention and management of cytomegalovirus (CMV) infections in pediatric hematopoietic stem cell transplant (HCT) recipients. CMV-seropositivity in pediatric recipients/donors (R/D) is lower than in adults. Post-HCT CMV infection rates appear to follow the hierarchy: R+/D− > R+/D+ > R−/D+. Pediatric risk factors are similar to those seen in adults and include recipient CMV-seropositivity, HCT from an alternative donor, older age, and graft-versus-host-disease. In case of CMV-seropositive pediatric recipients, donor CMV-seronegativity is associated with lower survival and higher non-relapse mortality. Until recently, preemptive treatment has been the standard approach for managing pediatric post-HCT CMV infection. The successful introduction of letermovir in the prophylaxis of CMV infection has changed this approach and has become the standard of care in adults. Clinical data and recent FDA/EMA approval of letermovir in children are also providing a breakthrough in pediatric CMV disease prevention. Pre-emptive treatment remains the preferred approach in case of clinically significant CMV infection in both adults and children; meanwhile, new available options such as maribavir and broader application of viral-specific T-cells represent valid strategies for the management of refractory/resistant CMV infection, offering a less-toxic therapeutic alternative to conventional, still effective, antivirals.","PeriodicalId":9126,"journal":{"name":"Bone Marrow Transplantation","volume":"61 1","pages":"3-10"},"PeriodicalIF":5.2,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41409-025-02739-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145343288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-18DOI: 10.1038/s41409-025-02726-8
Arnon Nagler, Jacques-Emmanuel Galimard, Sarah Kayser, Alexander Kulagin, Didier Blaise, Elena Parovichnikova, Jurjen Versluis, Maija Itäla-Remes, Goda Choi, Rodrigo Martino Bufarull, Simona Sica, Mieke W. H. Roeven, Peter von dem Borne, Ali Bazarbachi, Jaime Sanz, Mohamad Mohty, Fabio Ciceri
We assessed pGF in 2497 AML patients undergoing HSCT from 8-10/10 HLA-matched UD with PTCy. pGF was defined as failure to achieve an ANC ≥ 0.5 × 109/L by day +30 after HSCT. The day +30 cumulative incidence of ANC was 92.6% (95%CI: 91.5–93.6), and the incidence of death without ANC recovery was 1.8% (95% CI: 1.3%–2.3%), corresponding to 141 (5.6%) patients not achieving an ANC ≥ 0.5 × 109/L by day +30. PB was the graft source in 89.4% of the patients, and 56% received reduced-intensity conditioning. 21 patients underwent a second HSCT (15 in the absence of ANC recovery and 6 after ANC recovery). 1-y NRM and RI post-pGF were 22.1% and 22.4%, respectively. 1-y LFS and OS post-pGF were 59% and 55.5%, respectively. ANC recovery evaluated as a time-dependent covariate, KPS ≥ 90, and being in CR at the time of HSCT were associated with improved OS. In conclusion, the incidence of pGF post-unrelated HSCT with PTCy was 5.6%. Of the patients who failed to engraft by day +30, 70.9% did so by day +60. A second transplant can save some of the patients with pGF.
{"title":"Outcomes of primary graft failure in acute myeloid leukemia patients following unrelated transplantation with post-transplant cyclophosphamide: a study from the ALWP/EBMT","authors":"Arnon Nagler, Jacques-Emmanuel Galimard, Sarah Kayser, Alexander Kulagin, Didier Blaise, Elena Parovichnikova, Jurjen Versluis, Maija Itäla-Remes, Goda Choi, Rodrigo Martino Bufarull, Simona Sica, Mieke W. H. Roeven, Peter von dem Borne, Ali Bazarbachi, Jaime Sanz, Mohamad Mohty, Fabio Ciceri","doi":"10.1038/s41409-025-02726-8","DOIUrl":"10.1038/s41409-025-02726-8","url":null,"abstract":"We assessed pGF in 2497 AML patients undergoing HSCT from 8-10/10 HLA-matched UD with PTCy. pGF was defined as failure to achieve an ANC ≥ 0.5 × 109/L by day +30 after HSCT. The day +30 cumulative incidence of ANC was 92.6% (95%CI: 91.5–93.6), and the incidence of death without ANC recovery was 1.8% (95% CI: 1.3%–2.3%), corresponding to 141 (5.6%) patients not achieving an ANC ≥ 0.5 × 109/L by day +30. PB was the graft source in 89.4% of the patients, and 56% received reduced-intensity conditioning. 21 patients underwent a second HSCT (15 in the absence of ANC recovery and 6 after ANC recovery). 1-y NRM and RI post-pGF were 22.1% and 22.4%, respectively. 1-y LFS and OS post-pGF were 59% and 55.5%, respectively. ANC recovery evaluated as a time-dependent covariate, KPS ≥ 90, and being in CR at the time of HSCT were associated with improved OS. In conclusion, the incidence of pGF post-unrelated HSCT with PTCy was 5.6%. Of the patients who failed to engraft by day +30, 70.9% did so by day +60. A second transplant can save some of the patients with pGF.","PeriodicalId":9126,"journal":{"name":"Bone Marrow Transplantation","volume":"61 1","pages":"51-58"},"PeriodicalIF":5.2,"publicationDate":"2025-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41409-025-02726-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145318047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-16DOI: 10.1038/s41409-025-02727-7
Arnon Nagler, Jordi Esteve, Jacques-Emmanuel Galimard, Jaime Sanz, Xavier Poire, Matthew Collin, Johan Maertens, He Huang, Maija Itäla-Remes, Khalid Halahleh, Maria Jesús Pascual Cascon, Patrizia Chiusolo, Laimonas Griskevicius, Ain Kaare, Ann De Becker, Pavel Jindra, Jose Antonio Pérez-Simón, Ali Bazarbachi, Eolia Brissot, Fabio Ciceri, Mohamad Mohty
We compared transplantation outcomes of AML patients with WT1 mutation (mWT1), identified by next-generation sequencing, to those of patients with wild-type WT1 AML (wtWT1). 703 patients were included, 50 with mWT1 and 653 with wtWT1. Patients with mWT1 were younger (median age: 45.6 vs. 56.4 years, p < 0.001), with a higher proportion of females (66% vs. 47.6%, p = 0.01), higher frequency of mutations in FLT3-ITD (38.3% vs. 21.7%, p = 0.01) and CEBPA (15.8% vs. 5.7%, p = 0.03). Donors were matched siblings in 30.6%, unrelated in 45.6%, and haploidentical in 22.1%. A higher percentage of mWT1 vs. wtWT1 patients received in vivo T-cell depletion (66% vs. 51%, p = 0.03) and 58% vs. 47.1% received myeloablative conditioning. 49 patients with mWT1 were matched to 127 wtWT1 patients in matched-pairs analysis. Outcomes (mWT1 vs. wtWT1) were not significantly different: relapse (2 y: 28.8% vs. 30.4%, HR: 1.14, p = 0.64), NRM (2 y: 15.5% vs. 9.9%, HR: 1.41, p = 0.49), LFS (2 y: 55.7% vs. 59.6%, HR: 1.21, p = 0.39), OS (2 y: 65.4% vs. 73.3%, p = 0.66), and chronic GVHD (2 y:24.3% vs. 25.4%, p = 0.95). In conclusion, WT1 mutation did not influence transplantation outcomes of AML patients in CR1.
我们比较了通过下一代测序鉴定的WT1突变（mWT1） AML患者与野生型WT1 AML （wtWT1）患者的移植结果。共纳入703例患者，其中mWT1 50例，wtWT1 653例。mWT1患者更年轻(中位年龄：45.6岁对56.4岁，p
{"title":"Impact of Wilms’ tumor 1 gene (WT1) mutation on outcome of allogeneic hematopoietic-cell transplantation for acute myeloid leukemia: a retrospective multicenter cohort study from the ALWP/EBMT registry","authors":"Arnon Nagler, Jordi Esteve, Jacques-Emmanuel Galimard, Jaime Sanz, Xavier Poire, Matthew Collin, Johan Maertens, He Huang, Maija Itäla-Remes, Khalid Halahleh, Maria Jesús Pascual Cascon, Patrizia Chiusolo, Laimonas Griskevicius, Ain Kaare, Ann De Becker, Pavel Jindra, Jose Antonio Pérez-Simón, Ali Bazarbachi, Eolia Brissot, Fabio Ciceri, Mohamad Mohty","doi":"10.1038/s41409-025-02727-7","DOIUrl":"10.1038/s41409-025-02727-7","url":null,"abstract":"We compared transplantation outcomes of AML patients with WT1 mutation (mWT1), identified by next-generation sequencing, to those of patients with wild-type WT1 AML (wtWT1). 703 patients were included, 50 with mWT1 and 653 with wtWT1. Patients with mWT1 were younger (median age: 45.6 vs. 56.4 years, p < 0.001), with a higher proportion of females (66% vs. 47.6%, p = 0.01), higher frequency of mutations in FLT3-ITD (38.3% vs. 21.7%, p = 0.01) and CEBPA (15.8% vs. 5.7%, p = 0.03). Donors were matched siblings in 30.6%, unrelated in 45.6%, and haploidentical in 22.1%. A higher percentage of mWT1 vs. wtWT1 patients received in vivo T-cell depletion (66% vs. 51%, p = 0.03) and 58% vs. 47.1% received myeloablative conditioning. 49 patients with mWT1 were matched to 127 wtWT1 patients in matched-pairs analysis. Outcomes (mWT1 vs. wtWT1) were not significantly different: relapse (2 y: 28.8% vs. 30.4%, HR: 1.14, p = 0.64), NRM (2 y: 15.5% vs. 9.9%, HR: 1.41, p = 0.49), LFS (2 y: 55.7% vs. 59.6%, HR: 1.21, p = 0.39), OS (2 y: 65.4% vs. 73.3%, p = 0.66), and chronic GVHD (2 y:24.3% vs. 25.4%, p = 0.95). In conclusion, WT1 mutation did not influence transplantation outcomes of AML patients in CR1.","PeriodicalId":9126,"journal":{"name":"Bone Marrow Transplantation","volume":"61 1","pages":"44-50"},"PeriodicalIF":5.2,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41409-025-02727-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145306679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-15DOI: 10.1038/s41409-025-02732-w
Patryk Sobieralski, Tomasz Czerw, Luuk Gras, Linda Koster, Nicolaus Kröger, Thomas Schroeder, Lone Friis, Elisabetta Metafuni, Jakob Passweg, Marie Robin, Matthias Stelljes, Annoek E. C. Broers, Patrice Chevallier, Robert Zeiser, Marie Therese Rubio, Mareike Verbeek, Ipek Yonal-Hindilerden, Domenico Pastore, Jan Zaucha, Kavita Raj, Joanna Drozd-Sokołowska, Giorgia Battipaglia, Nicola Polverelli, Juan Carlos Hernández-Boluda, Donal P. McLornan
Outcomes in myelofibrosis (MF) patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) appear unaffected by the intensity of the preparative regimen, defined traditionally as myeloablative (MAC) or reduced intensity conditioning (RIC). The Transplant Conditioning Intensity (TCI) index is an objective tool offering a precise measure of conditioning intensity. We explored the potential association between TCI score and overall survival (OS), progression-free survival (PFS), cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) in 2454 MF patients undergoing allo-HCT between 2012 and 2021, selected from the EBMT registry. Patients receiving TCI-intermediate/high regimens had similar OS (HR 1.12, 95% CI 0.97–1.30) and PFS (HR 1.00, 95% CI 0.88–1.14) compared to TCI-low regimens. However, TCI-intermediate/high regimens were associated with lower risk of relapse (HR 0.74, 95% CI 0.61–0.91, p = 0.008) and higher risk of NRM (HR 1.24, 95% CI 1.04–1.48, p = 0.02). Our findings suggest that the TCI score provides a more clinically relevant stratification of conditioning intensity than the conventional MAC/RIC classification. While higher intensity TCI regimens are associated with lower RI, this benefit is offset by increased NRM, resulting in no survival advantage. However, the TCI index may enable a more personalized approach to conditioning regimen selection by balancing relapse risk with patient frailty.
骨髓纤维化（MF）患者接受同种异体造血细胞移植（allogenic hematopoietic cell transplantation, alloo - hct）的结果似乎不受预备方案强度的影响，传统上定义为骨髓清除（MAC）或降低强度调节（RIC）。移植调节强度（TCI）指数是提供调节强度精确测量的客观工具。我们从EBMT注册表中选择了2454例2012年至2021年间接受异位肝移植的MF患者，探讨了TCI评分与总生存期（OS）、无进展生存期（PFS）、累积复发发生率（CIR）和非复发死亡率（NRM）之间的潜在关联。与低tci方案相比，接受tci中高方案的患者具有相似的OS （HR 1.12, 95% CI 0.97-1.30）和PFS （HR 1.00, 95% CI 0.88-1.14）。然而，tci -中/高方案与较低的复发风险（HR 0.74, 95% CI 0.61-0.91, p = 0.008）和较高的NRM风险（HR 1.24, 95% CI 1.04-1.48, p = 0.02）相关。我们的研究结果表明，与传统的MAC/RIC分类相比，TCI评分提供了更具有临床相关性的调节强度分层。虽然高强度TCI方案与较低的RI相关，但这种益处被增加的NRM抵消，导致没有生存优势。然而，TCI指数可以通过平衡复发风险和患者虚弱来实现更个性化的治疗方案选择。
{"title":"Transplant conditioning intensity (TCI) score predicts allo-HCT outcomes in patients with myelofibrosis: a study of the Chronic Malignancies Working Party of EBMT","authors":"Patryk Sobieralski, Tomasz Czerw, Luuk Gras, Linda Koster, Nicolaus Kröger, Thomas Schroeder, Lone Friis, Elisabetta Metafuni, Jakob Passweg, Marie Robin, Matthias Stelljes, Annoek E. C. Broers, Patrice Chevallier, Robert Zeiser, Marie Therese Rubio, Mareike Verbeek, Ipek Yonal-Hindilerden, Domenico Pastore, Jan Zaucha, Kavita Raj, Joanna Drozd-Sokołowska, Giorgia Battipaglia, Nicola Polverelli, Juan Carlos Hernández-Boluda, Donal P. McLornan","doi":"10.1038/s41409-025-02732-w","DOIUrl":"10.1038/s41409-025-02732-w","url":null,"abstract":"Outcomes in myelofibrosis (MF) patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) appear unaffected by the intensity of the preparative regimen, defined traditionally as myeloablative (MAC) or reduced intensity conditioning (RIC). The Transplant Conditioning Intensity (TCI) index is an objective tool offering a precise measure of conditioning intensity. We explored the potential association between TCI score and overall survival (OS), progression-free survival (PFS), cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) in 2454 MF patients undergoing allo-HCT between 2012 and 2021, selected from the EBMT registry. Patients receiving TCI-intermediate/high regimens had similar OS (HR 1.12, 95% CI 0.97–1.30) and PFS (HR 1.00, 95% CI 0.88–1.14) compared to TCI-low regimens. However, TCI-intermediate/high regimens were associated with lower risk of relapse (HR 0.74, 95% CI 0.61–0.91, p = 0.008) and higher risk of NRM (HR 1.24, 95% CI 1.04–1.48, p = 0.02). Our findings suggest that the TCI score provides a more clinically relevant stratification of conditioning intensity than the conventional MAC/RIC classification. While higher intensity TCI regimens are associated with lower RI, this benefit is offset by increased NRM, resulting in no survival advantage. However, the TCI index may enable a more personalized approach to conditioning regimen selection by balancing relapse risk with patient frailty.","PeriodicalId":9126,"journal":{"name":"Bone Marrow Transplantation","volume":"61 1","pages":"36-43"},"PeriodicalIF":5.2,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41409-025-02732-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145298500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-13DOI: 10.1038/s41409-025-02733-9
James Fan Wu, Noel Estrada-Merly, Yuhong Zhou, Bethany Canales, Tina W. F. Yen, Anita D’Souza
{"title":"Multiple myeloma incidence, transplant utilization, and mortality- impact of social vulnerability","authors":"James Fan Wu, Noel Estrada-Merly, Yuhong Zhou, Bethany Canales, Tina W. F. Yen, Anita D’Souza","doi":"10.1038/s41409-025-02733-9","DOIUrl":"10.1038/s41409-025-02733-9","url":null,"abstract":"","PeriodicalId":9126,"journal":{"name":"Bone Marrow Transplantation","volume":"61 1","pages":"95-97"},"PeriodicalIF":5.2,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12590446/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145285609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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